WO2009144977A1 - Oral composition for hair growth - Google Patents

Oral composition for hair growth Download PDF

Info

Publication number
WO2009144977A1
WO2009144977A1 PCT/JP2009/053091 JP2009053091W WO2009144977A1 WO 2009144977 A1 WO2009144977 A1 WO 2009144977A1 JP 2009053091 W JP2009053091 W JP 2009053091W WO 2009144977 A1 WO2009144977 A1 WO 2009144977A1
Authority
WO
WIPO (PCT)
Prior art keywords
hair
composition
sialic acid
oral
hair growth
Prior art date
Application number
PCT/JP2009/053091
Other languages
French (fr)
Japanese (ja)
Inventor
研二 岡嶋
直明 原田
信也 山口
泰弘 太田
Original Assignee
ジャパン・フード＆リカー・アライアンス株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ジャパン・フード＆リカー・アライアンス株式会社 filed Critical ジャパン・フード＆リカー・アライアンス株式会社
Priority to JP2010514394A priority Critical patent/JPWO2009144977A1/en
Publication of WO2009144977A1 publication Critical patent/WO2009144977A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • the present invention relates to a composition for oral hair restoration.
  • this invention relates to the composition for oral hair growth which contains sialic acid as an active ingredient and has a hair growth effect.
  • hair growth agents have been developed so far, most of which are rubbed into the scalp and gained its effectiveness through penetration from the scalp. Such a usage method is difficult to use easily and makes it difficult to continue using it. In addition, many of them are traded at a high price, which places a burden on the therapist in terms of cost.
  • a hair growth agent that is orally administered or ingested has also been developed.
  • anti-hair loss symptom food and drink containing oolong tea extract containing oolong tea extract
  • oral anti-hair loss symptom agent Patent Document 1
  • hair growth food containing proanthocyanidins Patent Document 2
  • Non-patent Document 3 capsaicin is a substance that temporarily gives severe irritation to the digestive organs such as the stomach and esophagus, and depending on the person, the digestive organs such as the stomach may be affected by ingestion.
  • capsaicin is a substance that temporarily gives severe irritation to the digestive organs such as the stomach and esophagus, and depending on the person, the digestive organs such as the stomach may be affected by ingestion.
  • due to the stimulation there is a problem that it is difficult to ingest unless it is ingested with a large amount of water.
  • JP-A-9-309840 Japanese Patent Laid-Open No. 2000-201650 Japanese Patent Laying-Open No. 2005-068129 Naoaki Harada et al., Growth Hormone & IGF Research 17 (2007) 408-415
  • An object of the present invention is to provide an oral hair-growth composition that has an excellent hair-growth effect and does not cause intense irritation to the digestive organs upon administration or ingestion.
  • the present inventors can obtain an excellent hair-growth effect by oral administration or ingestion of sialic acid, and are accompanied by irritation to the digestive organs even when oral administration or ingestion of sialic acid.
  • the inventors have found that the present invention can solve the above-mentioned problems.
  • the present invention includes the following oral hair restoration compositions, hair restoration methods, oral hair restoration agents and the like according to items 1 to 19 below.
  • Item 1. An oral hair restoration composition comprising sialic acid and a pharmaceutically acceptable or ingestible carrier.
  • Item 2. The composition for oral hair restoration according to Item 1, wherein the sialic acid is N-acetylneuraminic acid.
  • Item 3. The composition for oral hair restoration according to Item 1 or 2, comprising 0.1 to 95% by weight of sialic acid.
  • Item 4. Item 4. The composition for oral hair restoration according to any one of Items 1 to 3, which is administered or ingested in an amount of 0.01 to 1000 mg / kg (body weight) per day for an adult.
  • Item 5. Item 5.
  • Item 5. The composition for oral hair restoration according to any one of Items 1 to 4, which is a food composition.
  • Item 7. A method for hair growth comprising the step of orally administering or ingesting a person who desires hair growth with an amount of sialic acid effective for hair growth.
  • Item 8. The hair growth method according to Item 7, wherein the sialic acid is N-acetylneuraminic acid.
  • sialic acid is administered or ingested in an amount of 0.01 to 1000 mg / kg (body weight) per day.
  • Item 10. Use of sialic acid for the production of a composition for oral hair restoration.
  • Item 11. Item 11. The use according to Item 10, wherein the sialic acid is N-acetylneuraminic acid.
  • Item 12. Sialic acid for hair growth by oral administration or ingestion.
  • Item 13. N-acetylneuraminic acid for hair growth by oral administration or ingestion.
  • Item 14. Item 5. The oral hair growth composition according to any one of Items 1 to 4, which is a food additive for hair growth.
  • Item 16. Item 16.
  • Item 17. Item 17.
  • Item 18. An oral hair restorer comprising a food composition containing sialic acid.
  • Item 19. An oral hair restorer comprising a food composition containing sialic acid.
  • CGRP calcitonin gene-related peptide
  • IGF-I insulin-like growth factor-I
  • an oral hair growth composition an oral hair growth agent, and a hair growth method that have an excellent hair growth effect and that do not cause irritation to the digestive organs by oral administration or ingestion.
  • the hair-growth effect refers to the effect of growing hair, and the effect of growing hair such as thickening, lengthening, strengthening, making it difficult to remove, and growing (stretching) the hair.
  • the present invention is particularly excellent in the effect of growing hair.
  • composition for oral hair restoration according to the present invention is characterized by containing sialic acid as an active ingredient.
  • Sialic acid is a generic name for substances in which the amino group or hydroxy group of neuraminic acid is substituted.
  • the sialic acid used in the composition for oral hair restoration according to the present invention may be naturally derived or chemically synthesized.
  • naturally-derived materials not only purified products but also crude products can be used as long as the effects of the present invention can be obtained.
  • Examples of naturally derived substances containing a large amount of sialic acid include axilla, milk, egg yolk and the like, and axilla is particularly preferable because of its high sialic acid content.
  • milk and egg yolk are preferable from the ease of acquisition.
  • Sialic acid can also be produced by, for example, an enzyme synthesis method using glucosamine as a raw material, a genetic engineering method using Escherichia coli, or the like, and these can also be used in the present invention.
  • sialic acids can be used singly or in appropriate combination of two or more.
  • composition for oral hair restoration according to the present invention contains, in addition to sialic acid, a pharmaceutically acceptable carrier or an ingestible carrier.
  • the amount of sialic acid can be appropriately set according to the daily administration or intake amount, etc., but is preferably 0.01 to 99% by weight, more preferably 0.1 to 95% by weight based on the whole composition. 1 to 90% by weight is more preferable.
  • the composition for oral hair restoration according to the present invention has an effect of inducing the release of calcitonin gene-related peptide (CGRP) and promoting the production of IGF-I within a range not losing the effects of the present invention. May be combined with sialic acid.
  • IGF-I production promoting component include capsaicin, isoflavone, raspberry ketone, capsiate, honey, royal jelly, and the like. Among these, isoflavone is preferable.
  • the compounding amount of the IGF-I production promoting component can be appropriately set according to the form of the oral hair growth composition according to the present application, the daily administration or intake amount, and the like.
  • an IGF-I production promoting component By blending an IGF-I production promoting component, a synergistic hair growth effect with sialic acid can be expected. In particular, those blended at a ratio of 0.25 to 0.75 parts by weight of isoflavone to 1 part by weight of sialic acid are preferred, and those blended at 0.5 parts by weight are particularly preferred.
  • the IGF-I production promoting component can be used alone or in combination of two or more in combination with sialic acid.
  • composition for oral hair restoration according to the present invention, a pharmaceutically acceptable or ingestible carrier can be blended within a range that does not impair the effects of the present invention.
  • Examples of pharmaceutically acceptable carriers include excipients, diluents, binders, disintegrants, stabilizers, absorption promoters, humectants, adsorbents, lubricants, and the like. Moreover, these agents can be illustrated as an ingestible carrier, for example. These carriers can be used singly or in appropriate combination of two or more.
  • the fluorescent hair-growth composition according to the present invention can be blended with optional components as long as the effects of the present invention are not impaired.
  • Such ingredients include, for example, antioxidants, coloring agents, sugar coatings, coating agents, pH regulators, emulsifiers, preservatives, sweeteners, preservatives, chewing agents, cooling agents, feeding accelerators, potentiators. Examples thereof include a sticky agent, a fragrance, a dispersant, and a miso odorant.
  • optional components can be used singly or in appropriate combination of two or more.
  • the oral hair growth composition according to the present invention is preferably, for example, a pharmaceutical composition or a food composition.
  • the carrier to be blended is preferably pharmaceutically acceptable.
  • the carrier is pharmaceutically acceptable or ingestible. Preferably there is.
  • the shape of the composition for oral hair restoration according to the present invention is not particularly limited as long as it can be administered orally.
  • it can be used as a liquid solution or as a solid tablet, powder, granule, powder or the like.
  • such an oral hair growth composition can be used as a pharmaceutical composition or a food composition for hair growth.
  • it can utilize also as a food additive for hair growth used by adding to food.
  • the amount added to the food is appropriately set, and the food added with the food additive is eaten. Ingest.
  • the said addition may be performed during food preparation or manufacture, and may be performed when eating the cooked food.
  • Examples of such food additives include, but are not limited to, liquids, powders, flakes, granules, and pastes.
  • composition for oral hair restoration according to the present invention is a food composition
  • ingredients used as food may be blended within a range that does not impair the effects of the present invention. it can.
  • the food composition include sialic acid-containing foods such as axilla, milk and egg yolk, various foods artificially containing sialic acid, and food compositions produced using these.
  • the kind of food composition of this invention is not specifically limited, For example, drinks, confectionery (for example, gum, chocolate, candy, biscuits, cookies, rice crackers, rice crackers, etc.), breads, soups (powder soup, etc.) Etc.) can be exemplified.
  • the food composition of the present invention can also be prepared as health foods (nutrient functional foods, foods for specified health use, etc.), supplements, foods for the sick, etc. for hair growth purposes.
  • health foods nutrient functional foods, foods for specified health use, etc.
  • supplements foods for the sick, etc. for hair growth purposes.
  • the food composition of the present invention in order to facilitate continuous intake, for example, in the form of granules, capsules, tablets (including chewable agents), beverages (drinks), etc. It is desirable to prepare, and in particular, capsules, tablets, and tablets are preferable from the viewpoint of easy intake, but are not particularly limited thereto.
  • the food and beverage composition of the present invention in the form of capsules and tablets can be appropriately prepared according to a conventional method using the pharmaceutically acceptable carrier. Moreover, even if it is a case where it prepares in another form, what is necessary is just to follow the conventional method.
  • the composition for oral hair restoration according to the present invention can be administered or ingested for the purpose of hair restoration.
  • humans who desire hair growth can be suitably used.
  • humans who desire hair growth include those who suffer from hair loss and thinning hair, those who suffer from hair-related diseases such as alopecia, and those who have hair loss due to side effects of drugs.
  • humans who desire further hair growth and hair growth can also be used without worrying about these symptoms.
  • it can be applied not only to humans but also to pets, livestock and the like for which hair growth is desired. In this case, it can be used as a hair growth additive for pets and livestock medicines, solid and powdered feeds, and the like.
  • the effective administration or intake for hair restoration of the composition for oral hair restoration according to the present invention is preferably 0.01 to 1000 mg / kg (body weight) / day in terms of sialic acid when used by an adult, and 0.1 to 100 mg. / kg (weight) / day is more preferable.
  • the composition for oral hair restoration can be administered or ingested once or twice a day, and is preferably administered or ingested 1 to 3 times a day.
  • the administration or intake of a child or pet who desires hair growth can be appropriately set according to the shape of the agent, the strength of the effect, and the like.
  • the present invention also provides an oral hair restorer containing sialic acid as an active ingredient.
  • the oral hair restorer can take, for example, the same form as that of the aforementioned oral hair restorer composition. Moreover, the said oral hair restorer may consist only of sialic acid.
  • the present invention also provides a hair-growth method characterized by orally administering or ingesting sialic acid to a human suffering from hair loss or thinning hair, or a human who desires hair growth. Specifically, this method is carried out by administering or ingesting the above-mentioned composition for oral hair restoration.
  • each condition such as the type of sialic acid, oral administration or intake is as described above.
  • Test Example 1 Preparation of mouse dorsal root ganglion cells (DRG) 6- to 8-week-old C57BL / 6 male mice (Japan SLC) were prepared to be ketalal 100 mg / kg and xylazine 10 mg / kg. The mixture was administered intraperitoneally and anesthetized. The cervical vertebrae to lumbar vertebrae were removed, separated in the midline, and bilateral DRGs were collected.
  • DRG mouse dorsal root ganglion cells
  • the extracted DRG is put in 1.6 ml collagenase II (manufactured by GIBCO), 100 U / ml dispase I (manufactured by Godo Shusei), and 5% fetal bovine serum (FBS) -containing Minimum Essential Medium (manufactured by GIBCO) It was left overnight at 37 ° C., 5% CO 2 . After completion, the mixture was centrifuged at 3000 rpm and 25 ° C. for 5 minutes, and the supernatant was discarded. A nutrient solution having the following composition was added to the cells, stirred uniformly, and then cultured for 7 days at 37 ° C. and 5% CO 2 using a 35 mm dish (manufactured by BD Japan) coated with collagen I.
  • DMEM / F-12 medium Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 mixed 1: 1) containing the following was used as a nutrient solution.
  • Test Example 2 Effect of sialic acid on CGRP release from mouse dorsal root ganglion cells (DRG) After culturing DRG for 7 days as described in Test Example 1, the nutrient solution was discarded on the 7th day of culture, Replaced with DMEM / F-12 containing 1% FBS. N-acetylneuraminic acid (manufactured by Japan Food & Liquor Alliance) prepared so as to have final concentrations of 1, 10 and 100 mM was added thereto and left at 37 ° C. and 5% CO 2 for 30 minutes. After completion, the culture supernatant was collected and stored at -20 ° C. The CGRP concentration in the culture supernatant was measured using an ELISA kit (manufactured by SPI bio). The results are shown in FIG.
  • DRG mouse dorsal root ganglion cells
  • N-acetylneuraminic acid has an action of stimulating sensory nerves and releasing CGRP. It was also found that the higher the concentration of N-acetylneuraminic acid, the greater the amount of CGRP released (p ⁇ 0.01).
  • composition for oral hair restoration according to the present application can be obtained by the production and release of CGRP.
  • Test Example 3 Hair growth effect of sialic acid 6-week-old C57BL / 6 male mice (Japan SLC) were administered intraperitoneally with a mixture prepared to give ketalal 100 mg / kg and xylazine 10 mg / kg After anesthesia, the back was shaved with a size of 2 ⁇ 4 cm. Next, N-acetylneuraminic acid was dissolved in physiological saline so as to be 0.25 mg / ml and 0.5 mg / ml.
  • mice forcibly administered once a day into the stomach of the aforementioned shaved mouse using a gastric sonde so as to be 0.1 ml per 10 g of body weight ie, the final dose was 2.5 mg / kg / day and 5 mg / day). kg / day).
  • the control shaved mouse was administered with physiological saline so as to be 0.1 ml per 10 g of body weight.
  • mice forcibly administered with these N-acetylneuraminic acids and the control mice forcibly administered with only saline were bred under the following conditions except for the forcible administration.
  • the control mice have almost no hair on the shaved part, whereas the N-acetylneuraminic acid 2.5 mg / kg / day group has some hair and has a shaved part. Furthermore, in the 5 mg / kg / day administration group, hair was grown to such an extent that the shaved portion was hardly visible.
  • Test Example 4 Effect of sialic acid on mouse skin calcitonin gene-related peptide (CGRP) and insulin-like growth factor-I (IGF-I) concentrations ⁇ Skin sample collection> N-acetylneuraminic acid was dissolved in physiological saline to a concentration of 0.5 mg / ml. Then, using a gastric sonde, this was forcibly administered once a day into the stomach of 6 to 8 week old C57BL / 6 male mice (5 mice) to 0.1 ml per 10 g of body weight (ie, the final dose was 5 mg / kg / day). Similarly, physiological saline was administered to the control group so as to be 0.1 ml per 10 g of body weight (5 animals).
  • CGRP mouse skin calcitonin gene-related peptide
  • IGF-I insulin-like growth factor-I
  • mice forcibly administered with these N-acetylneuraminic acids and the control mice forcibly administered with only saline were bred under the conditions shown in Test Example 3 except for the forcible administration.
  • the skin CGRP concentration in the N-acetylneuraminic acid administration group is about 2.5 times that of the control group, and the skin IGF-I concentration is about 3 times that of the control group. became.
  • both the skin CGRP concentration and the skin IGF-I concentration were significantly higher in the N-acetylneuraminic acid administration group (p ⁇ 0.01).

Abstract

Provided is an oral composition for hair growth that has excellent hair growth efficacy, and for which administration or ingestion is not accompanied by severe irritation of the digestive organs. Provided is an oral composition for hair growth that comprises sialic acid and a pharmacologically allowable or edible carrier.

Description

経口育毛用組成物Oral hair growth composition
　本発明は、経口育毛用組成物に関する。詳細には、本発明は、シアル酸を有効成分として含有し、育毛効果を奏する経口育毛用組成物に関する。 The present invention relates to a composition for oral hair restoration. In detail, this invention relates to the composition for oral hair growth which contains sialic acid as an active ingredient and has a hair growth effect.
　様々なストレスや高齢化等の問題を抱える現代社会においては、脱毛や薄毛に悩む人々の数が増加しており、これを予防または治療し、さらに毛髪の伸長を促進しうるような育毛剤が、性別や年齢に関わりなく求められている。 In modern society with various problems such as stress and aging, the number of people suffering from hair loss and thinning hair is increasing, and there are hair restorers that can prevent or treat this and promote hair elongation. , Regardless of gender or age.
　これまでにも、様々な育毛剤が開発されてきたが、その大半は、頭皮に擦り込み、頭皮からの浸透によってその効能を得るものである。このような使用方式では手軽に利用しづらく、継続使用することを困難としている。また、高額な値段で取引されるものが多く、コスト面でも治療者に負担を強いている。 A variety of hair growth agents have been developed so far, most of which are rubbed into the scalp and gained its effectiveness through penetration from the scalp. Such a usage method is difficult to use easily and makes it difficult to continue using it. In addition, many of them are traded at a high price, which places a burden on the therapist in terms of cost.
　経口的に投与又は摂取する育毛剤、いわゆる経口育毛剤も開発がなされている。例えば、ウーロン茶抽出物を含む抗脱毛症状飲食物および経口抗脱毛症状剤（特許文献１）、プロアントシアニジンを含む育毛食品（特許文献２）等が知られている。 A hair growth agent that is orally administered or ingested, so-called oral hair growth agents, has also been developed. For example, anti-hair loss symptom food and drink containing oolong tea extract, oral anti-hair loss symptom agent (Patent Document 1), hair growth food containing proanthocyanidins (Patent Document 2) and the like are known.
　また、近年、カプサイシン感受性知覚神経におけるカルシトニン遺伝子関連ペプチド（CGRP）の産生および放出により、育毛効果が得られるとの報告がなされている（非特許文献１）。そこで、カプサイシンを経口摂取することで、育毛効果を得ようとする試みもなされている（特許文献３）。しかし、カプサイシンは、胃や食道をはじめとする消化器官に対し一時的に激しい刺激を与える物質であるため、人によっては、摂取により胃等の消化器官が不調をきたす場合があった。また、その刺激のために、多量の水とともに摂取しないと摂取しづらい場合がある等の問題もあった。
特開平９－３０９８４０号公報 特開２０００－２０１６５０号公報 特開２００５－０６８１２９号公報 Naoaki Harada et al., Growth Hormone & IGF Research 17 (2007) 408-415 In recent years, it has been reported that a hair-growth effect can be obtained by producing and releasing a calcitonin gene-related peptide (CGRP) in capsaicin-sensitive sensory nerves (Non-patent Document 1). Therefore, attempts have been made to obtain a hair-growth effect by ingesting capsaicin (Patent Document 3). However, capsaicin is a substance that temporarily gives severe irritation to the digestive organs such as the stomach and esophagus, and depending on the person, the digestive organs such as the stomach may be affected by ingestion. In addition, due to the stimulation, there is a problem that it is difficult to ingest unless it is ingested with a large amount of water.
JP-A-9-309840 Japanese Patent Laid-Open No. 2000-201650 Japanese Patent Laying-Open No. 2005-068129 Naoaki Harada et al., Growth Hormone & IGF Research 17 (2007) 408-415
　本発明は、優れた育毛効果を有し、かつ、投与又は摂取により消化器官への激しい刺激を伴わない、経口育毛用組成物を提供することを課題とする。 An object of the present invention is to provide an oral hair-growth composition that has an excellent hair-growth effect and does not cause intense irritation to the digestive organs upon administration or ingestion.
　本発明者らは、驚くべき事に、シアル酸を経口投与又は摂取することで、優れた育毛効果を得られること、また、シアル酸を経口投与又は摂取しても消化器官への刺激を伴わないこと、を見出し、上記課題を解決できる本発明を完成させるに至った。 Surprisingly, the present inventors can obtain an excellent hair-growth effect by oral administration or ingestion of sialic acid, and are accompanied by irritation to the digestive organs even when oral administration or ingestion of sialic acid. The inventors have found that the present invention can solve the above-mentioned problems.
　すなわち、本発明は、以下の項１～１９の経口育毛用組成物、育毛方法、経口育毛剤等を包含する。
項１．シアル酸、及び薬学的に許容される又は摂食可能な担体を含有する経口育毛用組成物。
項２．シアル酸がＮ－アセチルノイラミン酸である、項１に記載の経口育毛用組成物。
項３．シアル酸を0.1～95重量％含有する、項１又は２に記載の経口育毛用組成物。
項４．成人一日当たり0.01～1000mg/kg（体重）の量にて投与又は摂取される、項１～３のいずれかに記載の経口育毛用組成物。
項５．医薬組成物である、項１～４のいずれかに記載の経口育毛用組成物。
項６．食品組成物である、項１～４のいずれかに記載の経口育毛用組成物。
項７．育毛に有効な量のシアル酸を、育毛を望む人に経口投与又は摂取させる工程を含む、育毛方法。
項８.シアル酸がＮ－アセチルノイラミン酸である、項７に記載の育毛方法。
項９.シアル酸を、一日当たり0.01～1000mg/kg（体重）の量投与又は摂取させる、項７又は８に記載の育毛方法。
項１０．シアル酸の、経口育毛用組成物の製造のための使用。
項１１．シアル酸がＮ－アセチルノイラミン酸である、項１０に記載の使用。
項１２．経口投与又は摂取により育毛するためのシアル酸。
項１３．経口投与又は摂取により育毛するためのＮ－アセチルノイラミン酸。
項１４．育毛用の食品添加剤である、項１～４のいずれかに記載の経口育毛用組成物。
項１５．シアル酸を有効成分として含有する経口育毛剤。
項１６．シアル酸がＮ－アセチルノイラミン酸である、項１５に記載の経口育毛剤。
項１７．育毛用の食品添加剤である、項１５又は１６に記載の経口育毛剤。
項１８．シアル酸を含有する食品組成物を含んでなる経口育毛剤。
項１９．シアル酸を含有する食品組成物からなる経口育毛剤。 That is, the present invention includes the following oral hair restoration compositions, hair restoration methods, oral hair restoration agents and the like according to items 1 to 19 below.
Item 1. An oral hair restoration composition comprising sialic acid and a pharmaceutically acceptable or ingestible carrier.
Item 2. Item 2. The composition for oral hair restoration according to Item 1, wherein the sialic acid is N-acetylneuraminic acid.
Item 3. Item 3. The composition for oral hair restoration according to Item 1 or 2, comprising 0.1 to 95% by weight of sialic acid.
Item 4. Item 4. The composition for oral hair restoration according to any one of Items 1 to 3, which is administered or ingested in an amount of 0.01 to 1000 mg / kg (body weight) per day for an adult.
Item 5. Item 5. The composition for oral hair restoration according to any one of Items 1 to 4, which is a pharmaceutical composition.
Item 6. Item 5. The composition for oral hair restoration according to any one of Items 1 to 4, which is a food composition.
Item 7. A method for hair growth comprising the step of orally administering or ingesting a person who desires hair growth with an amount of sialic acid effective for hair growth.
Item 8. The hair growth method according to Item 7, wherein the sialic acid is N-acetylneuraminic acid.
Item 9. The hair growth method according to Item 7 or 8, wherein sialic acid is administered or ingested in an amount of 0.01 to 1000 mg / kg (body weight) per day.
Item 10. Use of sialic acid for the production of a composition for oral hair restoration.
Item 11. Item 11. The use according to Item 10, wherein the sialic acid is N-acetylneuraminic acid.
Item 12. Sialic acid for hair growth by oral administration or ingestion.
Item 13. N-acetylneuraminic acid for hair growth by oral administration or ingestion.
Item 14. Item 5. The oral hair growth composition according to any one of Items 1 to 4, which is a food additive for hair growth.
Item 15. An oral hair restorer containing sialic acid as an active ingredient.
Item 16. Item 16. The oral hair restorer according to Item 15, wherein the sialic acid is N-acetylneuraminic acid.
Item 17. Item 17. The oral hair restorer according to Item 15 or 16, which is a food additive for hair growth.
Item 18. An oral hair restorer comprising a food composition containing sialic acid.
Item 19. An oral hair restorer comprising a food composition containing sialic acid.
　またさらに、本発明者らは、シアル酸を経口投与又は摂取することで、体内（特に皮膚）の細胞中のカルシトニン遺伝子関連ペプチド（CGRP）およびインスリン様成長因子-Ｉ（IGF-I）濃度が上昇することも見出した。従って、本発明は、シアル酸を有効成分として含有することを特徴とする経口のCGRP及び／又はIGF-I濃度上昇用組成物も提供する。 Still further, the present inventors orally administer or ingest sialic acid to reduce the concentration of calcitonin gene-related peptide (CGRP) and insulin-like growth factor-I (IGF-I) in cells in the body (particularly skin). I also found it to rise. Therefore, the present invention also provides a composition for increasing the oral CGRP and / or IGF-I concentration, which contains sialic acid as an active ingredient.
　本発明によれば、優れた育毛効果を有し、かつ、経口投与又は摂取により消化器官への刺激を伴わない経口育毛用組成物、経口育毛剤、及び育毛方法を提供することができる。 According to the present invention, it is possible to provide an oral hair growth composition, an oral hair growth agent, and a hair growth method that have an excellent hair growth effect and that do not cause irritation to the digestive organs by oral administration or ingestion.
  なお、本発明において育毛効果とは、毛を生えさせる効果、及び毛を太くする、長くする、強くする、抜けにくくする、成長させる（伸ばす）等、毛を育む効果全般をいう。なかでも、本発明は毛を成長させる効果が特に優れている。 に お い て In the present invention, the hair-growth effect refers to the effect of growing hair, and the effect of growing hair such as thickening, lengthening, strengthening, making it difficult to remove, and growing (stretching) the hair. Among these, the present invention is particularly excellent in the effect of growing hair.
　以下、本発明について、さらに詳細に説明する。 Hereinafter, the present invention will be described in more detail.
　本発明に係る経口育毛用組成物は、シアル酸を有効成分として含有することを特徴とするものである。 The composition for oral hair restoration according to the present invention is characterized by containing sialic acid as an active ingredient.
　シアル酸とは、ノイラミン酸(neuraminic acid) のアミノ基やヒドロキシ基が置換された物質を総称するファミリー名である。 Sialic acid is a generic name for substances in which the amino group or hydroxy group of neuraminic acid is substituted.
　本発明に係る経口育毛用組成物に用いるシアル酸は、天然由来のものでも、化学的に合成したものでもよい。天然由来のものを利用する場合、精製物のみならず、粗精製物であっても、本発明の効果を得られるものであれば利用することができる。シアル酸を多く含む天然由来のものとしては、燕窩、牛乳、卵黄等が例示でき、特に燕窩はシアル酸含有量が多く、好ましい。また、入手のし易さからは牛乳や卵黄が好ましい。 The sialic acid used in the composition for oral hair restoration according to the present invention may be naturally derived or chemically synthesized. When using naturally-derived materials, not only purified products but also crude products can be used as long as the effects of the present invention can be obtained. Examples of naturally derived substances containing a large amount of sialic acid include axilla, milk, egg yolk and the like, and axilla is particularly preferable because of its high sialic acid content. Moreover, milk and egg yolk are preferable from the ease of acquisition.
　また、シアル酸は、例えば、グルコサミンを原料とした酵素合成法や大腸菌等を用いた遺伝子工学的手法等により生産することもでき、これらも本発明に用いることができる。 Sialic acid can also be produced by, for example, an enzyme synthesis method using glucosamine as a raw material, a genetic engineering method using Escherichia coli, or the like, and these can also be used in the present invention.
　本発明に係る経口育毛用組成物に用いることのできるシアル酸の種類としては、特に限定されないが、例えば、N－アセチルノイラミン酸 (Neu5Ac) 、N－グライコリルノイラミン酸 (Neu5Gc)、デアミノノイラミン酸、2,3－デヒドロノイラミン酸、N－アセチル－2,7－アンヒドロノイラミン酸、これらのO-アセチル化体等が挙げられ、なかでもN－アセチルノイラミン酸、N－グライコリルノイラミン酸、デアミノノイラミン酸が好ましく、特にN－アセチルノイラミン酸が好ましい。本発明に係る経口育毛用組成物において、シアル酸は、1種単独で又は2種以上を適宜組み合わせて用いることができる。 The type of sialic acid that can be used in the composition for oral hair restoration according to the present invention is not particularly limited, and examples thereof include N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), Examples include aminoneuraminic acid, 2,3-dehydroneuraminic acid, N-acetyl-2,7-anhydroneuraminic acid, and O-acetylated compounds thereof. Among them, N-acetylneuraminic acid, N -Glycolyl neuraminic acid and deaminoneuraminic acid are preferred, and N-acetylneuraminic acid is particularly preferred. In the composition for oral hair restoration according to the present invention, sialic acids can be used singly or in appropriate combination of two or more.
　本発明に係る経口育毛用組成物は、シアル酸の他に、薬学的に許容される担体、又は摂食可能な担体（ingestible carrier）を含む。シアル酸の配合量は、1日あたりの投与又は摂取量等に応じて適宜設定することができるが、該組成物全体に対して0.01～99重量％が好ましく、0.1～95重量％がより好ましく、1～90重量％がさらに好ましい。 The composition for oral hair restoration according to the present invention contains, in addition to sialic acid, a pharmaceutically acceptable carrier or an ingestible carrier. The amount of sialic acid can be appropriately set according to the daily administration or intake amount, etc., but is preferably 0.01 to 99% by weight, more preferably 0.1 to 95% by weight based on the whole composition. 1 to 90% by weight is more preferable.
　また、本発明に係る経口育毛用組成物には、本発明の効果を失わない範囲において、カルシトニン遺伝子関連ペプチド（CGRP）の放出を誘導し、そしてIGF－Iの産生を促進させる効果を有する成分を、シアル酸と併せて配合してもよい。このようなIGF－I産生促進成分としては、例えば、カプサイシン、イソフラボン、ラズベリーケトン、カプシエイト、蜂蜜、ローヤルゼリー等を挙げることができ、なかでもイソフラボンが好ましい。IGF－I産生促進成分の配合量は、本願に係る経口育毛用組成物の形態や1日当たりの投与又は摂取量等に応じて適宜設定できる。IGF－I産生促進成分を配合することにより、シアル酸との相乗育毛効果が期待できる。特に、シアル酸１重量部に対し、イソフラボン0.25～0.75重量部の比率で配合したものが好ましく、0.5重量部配合したものが特に好ましい。なお、該IGF－I産生促進成分は、シアル酸に併せて、1種単独で又は2種以上を適宜組み合わせて用いることができる。 In addition, the composition for oral hair restoration according to the present invention has an effect of inducing the release of calcitonin gene-related peptide (CGRP) and promoting the production of IGF-I within a range not losing the effects of the present invention. May be combined with sialic acid. Examples of such IGF-I production promoting component include capsaicin, isoflavone, raspberry ketone, capsiate, honey, royal jelly, and the like. Among these, isoflavone is preferable. The compounding amount of the IGF-I production promoting component can be appropriately set according to the form of the oral hair growth composition according to the present application, the daily administration or intake amount, and the like. By blending an IGF-I production promoting component, a synergistic hair growth effect with sialic acid can be expected. In particular, those blended at a ratio of 0.25 to 0.75 parts by weight of isoflavone to 1 part by weight of sialic acid are preferred, and those blended at 0.5 parts by weight are particularly preferred. The IGF-I production promoting component can be used alone or in combination of two or more in combination with sialic acid.
　本発明に係る経口育毛用組成物には、本発明の効果を損なわない範囲において、薬学的に許容される、又は摂食可能な担体を配合できる。 In the composition for oral hair restoration according to the present invention, a pharmaceutically acceptable or ingestible carrier can be blended within a range that does not impair the effects of the present invention.
　薬学的に許容される担体としては、例えば、賦形剤、希釈剤、結合剤、崩壊剤、安定化剤、吸収促進剤、保湿剤、吸着剤、滑沢剤等が例示できる。また、摂食可能な担体としても、例えばこれらの剤を例示できる。当該担体は、1種単独で又は2種以上を適宜組み合わせて用いることができる。 Examples of pharmaceutically acceptable carriers include excipients, diluents, binders, disintegrants, stabilizers, absorption promoters, humectants, adsorbents, lubricants, and the like. Moreover, these agents can be illustrated as an ingestible carrier, for example. These carriers can be used singly or in appropriate combination of two or more.
　さらに、本発明に係る蛍光育毛用組成物には、本発明の効果を損なわない範囲において、任意成分を配合できる。このような成分としては、例えば、抗酸化剤、着色剤、糖衣剤、コーティング剤、ｐＨ調節剤、乳化剤、防腐剤、甘味剤、保存剤、咀嚼剤、清涼化剤、摂食促進剤、増粘剤、香料、分散剤、嬌味嬌臭剤、などが例示できる。これらの任意成分は、1種単独で又は2種以上を適宜組み合わせて用いることができる。 Furthermore, the fluorescent hair-growth composition according to the present invention can be blended with optional components as long as the effects of the present invention are not impaired. Such ingredients include, for example, antioxidants, coloring agents, sugar coatings, coating agents, pH regulators, emulsifiers, preservatives, sweeteners, preservatives, chewing agents, cooling agents, feeding accelerators, potentiators. Examples thereof include a sticky agent, a fragrance, a dispersant, and a miso odorant. These optional components can be used singly or in appropriate combination of two or more.
　本発明に係る経口育毛用組成物は、例えば医薬組成物又は食品組成物であることが好ましい。また、医薬組成物である場合は、配合される担体は薬学的に許容されるものであることが好ましく、食品組成物である場合は薬学的に許容されるもの、又は摂食可能なものであることが好ましい。 The oral hair growth composition according to the present invention is preferably, for example, a pharmaceutical composition or a food composition. In the case of a pharmaceutical composition, the carrier to be blended is preferably pharmaceutically acceptable. In the case of a food composition, the carrier is pharmaceutically acceptable or ingestible. Preferably there is.
　本発明に係る経口育毛用組成物は、経口投与又は摂取できる形状であれば、その形状は特に限定されない。例えば、液状の液剤等として、あるいは固形状の錠剤、粉剤、顆粒剤、散剤等として利用することができる。上述のように、このような経口育毛用組成物は、育毛用の医薬組成物又は食品組成物として利用できる。また、食品に添加して使用する、育毛用の食品添加剤としても利用できる。 The shape of the composition for oral hair restoration according to the present invention is not particularly limited as long as it can be administered orally. For example, it can be used as a liquid solution or as a solid tablet, powder, granule, powder or the like. As described above, such an oral hair growth composition can be used as a pharmaceutical composition or a food composition for hair growth. Moreover, it can utilize also as a food additive for hair growth used by adding to food.
　食品添加剤として用いる場合は、該経口育毛用組成物の形態、１日当たりの摂取量等に応じて、食品への添加量を適宜設定し、該食品添加剤が添加された食品を食べることにより摂取する。なお、当該添加は食品調理中又は製造中に行ってもよいし、調理済みの食品を食べるときに行ってもよい。このような食品添加剤の形態としては、例えば液状、粉末状、フレーク状、顆粒状、ペースト状のものが挙げられるがこれらに限定されない。 When used as a food additive, depending on the form of the oral hair restoration composition, the amount of intake per day, etc., the amount added to the food is appropriately set, and the food added with the food additive is eaten. Ingest. In addition, the said addition may be performed during food preparation or manufacture, and may be performed when eating the cooked food. Examples of such food additives include, but are not limited to, liquids, powders, flakes, granules, and pastes.
　また、本発明に係る経口育毛用組成物が食品組成物である場合は、上述した任意成分の他にも、本願発明の効果を損なわない範囲で、食品として利用される成分を配合することができる。当該食品組成物として例えば燕窩、牛乳、卵黄等のシアル酸含有食品、シアル酸を人工的に含有させた種々の食品、あるいはこれらを用いて製造した食品組成物等を例示できる。なお、本発明の食品組成物の種類は特に限定されないが、例えば、飲料、菓子類（例えばガム、チョコレート、キャンディー、ビスケット、クッキー、おかき、煎餅等）、パン類、スープ類（粉末スープ等を含む）等の各種飲食品を例示できる。 In addition, when the composition for oral hair restoration according to the present invention is a food composition, in addition to the above-mentioned optional components, ingredients used as food may be blended within a range that does not impair the effects of the present invention. it can. Examples of the food composition include sialic acid-containing foods such as axilla, milk and egg yolk, various foods artificially containing sialic acid, and food compositions produced using these. In addition, although the kind of food composition of this invention is not specifically limited, For example, drinks, confectionery (for example, gum, chocolate, candy, biscuits, cookies, rice crackers, rice crackers, etc.), breads, soups (powder soup, etc.) Etc.) can be exemplified.
　育毛を目的とする健康食品（栄養機能食品、特定保健用食品等）、サプリメント、病者用食品等として本発明の食品組成物を調製することもできる。このような食品として本発明の食品組成物を調製する場合は、継続的な摂取が行いやすいように、例えば顆粒、カプセル、錠剤（チュアブル剤等を含む）、飲料（ドリンク剤）等の形態で調製することが望ましく、なかでもカプセル、タブレット、錠剤の形態が摂取の簡便さの点からは好ましいが、特にこれに限定されるものではない。カプセル、錠剤形態の本発明の飲食品組成物は、前記薬学的に許容される担体を用いて、常法に従って適宜調製することができる。また、他の形態に調製する場合であっても、従来の方法に従えばよい。 The food composition of the present invention can also be prepared as health foods (nutrient functional foods, foods for specified health use, etc.), supplements, foods for the sick, etc. for hair growth purposes. When preparing the food composition of the present invention as such a food, in order to facilitate continuous intake, for example, in the form of granules, capsules, tablets (including chewable agents), beverages (drinks), etc. It is desirable to prepare, and in particular, capsules, tablets, and tablets are preferable from the viewpoint of easy intake, but are not particularly limited thereto. The food and beverage composition of the present invention in the form of capsules and tablets can be appropriately prepared according to a conventional method using the pharmaceutically acceptable carrier. Moreover, even if it is a case where it prepares in another form, what is necessary is just to follow the conventional method.
　本発明に係る経口育毛用組成物は、育毛を目的として投与又は摂取することができる。特に育毛を望むヒトは好適に利用できる。育毛を望むヒトとしては、例えば脱毛や薄毛に悩む人、脱毛症等の毛に関する病気に罹患している人、薬の副作用により脱毛している人などが挙げられる。また、特にこういった症状に悩んでいなくとも、さらなる発毛、育毛を望むヒトも利用できる。また、ヒト用としてのみならず、育毛が望まれるペットや家畜等に適用することもできる。この場合には、ペット及び家畜用医薬品、あるいは固形及び粉末飼料等への育毛用添加剤等として利用できる。 The composition for oral hair restoration according to the present invention can be administered or ingested for the purpose of hair restoration. In particular, humans who desire hair growth can be suitably used. Examples of humans who desire hair growth include those who suffer from hair loss and thinning hair, those who suffer from hair-related diseases such as alopecia, and those who have hair loss due to side effects of drugs. In addition, humans who desire further hair growth and hair growth can also be used without worrying about these symptoms. Moreover, it can be applied not only to humans but also to pets, livestock and the like for which hair growth is desired. In this case, it can be used as a hair growth additive for pets and livestock medicines, solid and powdered feeds, and the like.
　本発明に係る経口育毛用組成物の育毛に有効な投与又は摂取量としては、成人が使用する場合、シアル酸量に換算して0.01～1000mg/kg（体重）/dayが好ましく、0.1～100mg/kg（体重）/dayがより好ましい。該経口育毛用組成物は、1日1回又は２回以上に分けて投与又は摂取することができ、１日１～３回の投与又は摂取が好ましい。また、育毛を望む子供やペット等の投与又は摂取量も、該剤の形状や効果の強弱等に応じて適宜設定することができる。 The effective administration or intake for hair restoration of the composition for oral hair restoration according to the present invention is preferably 0.01 to 1000 mg / kg (body weight) / day in terms of sialic acid when used by an adult, and 0.1 to 100 mg. / kg (weight) / day is more preferable. The composition for oral hair restoration can be administered or ingested once or twice a day, and is preferably administered or ingested 1 to 3 times a day. In addition, the administration or intake of a child or pet who desires hair growth can be appropriately set according to the shape of the agent, the strength of the effect, and the like.
　なお、本発明は、シアル酸を有効成分として含有する経口育毛剤も提供する。当該経口育毛剤は、例えば、前述の経口育毛用組成物の形態と同様の形態をとることができる。また、当該経口育毛剤は、シアル酸のみからなるものであってもよい。 The present invention also provides an oral hair restorer containing sialic acid as an active ingredient. The oral hair restorer can take, for example, the same form as that of the aforementioned oral hair restorer composition. Moreover, the said oral hair restorer may consist only of sialic acid.
　本発明は、特に脱毛や薄毛に悩むヒト、育毛を望むヒトに、シアル酸を経口投与又は摂取することを特徴とする育毛方法も提供する。当該方法は、具体的には、前述の経口育毛用組成物を投与又は摂取することで実施される。なお、当該方法における、シアル酸の種類、経口投与又は摂取量等の各条件は前述の通りである。 The present invention also provides a hair-growth method characterized by orally administering or ingesting sialic acid to a human suffering from hair loss or thinning hair, or a human who desires hair growth. Specifically, this method is carried out by administering or ingesting the above-mentioned composition for oral hair restoration. In this method, each condition such as the type of sialic acid, oral administration or intake is as described above.
　以下、本発明を具体的に説明するが、本発明は下記の例に限定されるものではない。 Hereinafter, the present invention will be described in detail, but the present invention is not limited to the following examples.
　試験例１：マウス後根神経節細胞（DRG）の調製
　6-8週齢のC57BL/6雄性マウス（日本SLC社）に対し、ケタラール 100 mg/kg、キシラジン 10 mg/kgとなるよう調製した混合液を腹腔内投与し、麻酔した。頸椎から腰椎までを取り出し、正中で分離して、両側のDRGを採取した。取り出したDRGは、1.6ml collagenase II（GIBCO社製）、100 U/ml dispase I（合同酒精社製）、5% fetal bovine serum（FBS）含有のMinimum Essential Medium（GIBCO社製）に入れて、37℃、5% CO2で一晩放置した。終了後、3000rpm、25℃で5分間遠心し、上清を廃棄した。下記組成の栄養液を細胞に加え、均一に攪拌後、コラーゲンIでコーティングした35 mmディッシュ（日本BD社製）を用いて7日間、37℃、5% CO2で培養した。 Test Example 1: Preparation of mouse dorsal root ganglion cells (DRG) 6- to 8-week-old C57BL / 6 male mice (Japan SLC) were prepared to be ketalal 100 mg / kg and xylazine 10 mg / kg. The mixture was administered intraperitoneally and anesthetized. The cervical vertebrae to lumbar vertebrae were removed, separated in the midline, and bilateral DRGs were collected. The extracted DRG is put in 1.6 ml collagenase II (manufactured by GIBCO), 100 U / ml dispase I (manufactured by Godo Shusei), and 5% fetal bovine serum (FBS) -containing Minimum Essential Medium (manufactured by GIBCO) It was left overnight at 37 ° C., 5% CO 2 . After completion, the mixture was centrifuged at 3000 rpm and 25 ° C. for 5 minutes, and the supernatant was discarded. A nutrient solution having the following composition was added to the cells, stirred uniformly, and then cultured for 7 days at 37 ° C. and 5% CO 2 using a 35 mm dish (manufactured by BD Japan) coated with collagen I.
　＜栄養液＞
以下のものを含有するDMEM/F-12培地（Dulbecco’s Modified Eagle Medium: Nutrient Mixture F-12 を1:1 で混合したもの）を栄養液として使用した。 <Nutrient solution>
A DMEM / F-12 medium (Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 mixed 1: 1) containing the following was used as a nutrient solution.
　　100 ng/ml nerve growth factor（mouse ’s; Sigma社製）
　　100 U/ml penicillin G
　　100 mg/ml streptomycin
　　0.25 mg/ml amphotericin B
　　10% FBS 100 ng / ml nerve growth factor (mouse's; Sigma)
100 U / ml penicillin G
100 mg / ml streptomycin
0.25 mg / ml amphotericin B
10% FBS
　試験例２：マウス後根神経節細胞（DRG）からのCGRP放出におけるシアル酸の効果
  試験例１に記載のようにしてDRGを７日間培養した後、培養7日目に栄養液を廃棄し、1% FBS含有DMEM/F-12に置き換えた。そこに最終濃度が1、10および100 mMになるように調製したN－アセチルノイラミン酸（ジャパン・フード＆リカー・アライアンス社製）を加え、30分間37℃、5% CO2で放置した。終了後に培養上清を集め、-20℃で保存した。培養上清中のCGRP濃度は、ELISAキット（SPI bio社製）を用いて測定した。
結果を図１に示す。 Test Example 2: Effect of sialic acid on CGRP release from mouse dorsal root ganglion cells (DRG) After culturing DRG for 7 days as described in Test Example 1, the nutrient solution was discarded on the 7th day of culture, Replaced with DMEM / F-12 containing 1% FBS. N-acetylneuraminic acid (manufactured by Japan Food & Liquor Alliance) prepared so as to have final concentrations of 1, 10 and 100 mM was added thereto and left at 37 ° C. and 5% CO 2 for 30 minutes. After completion, the culture supernatant was collected and stored at -20 ° C. The CGRP concentration in the culture supernatant was measured using an ELISA kit (manufactured by SPI bio).
The results are shown in FIG.
　当該結果から、１～100μＭのN－アセチルノイラミン酸が、知覚神経を刺激し、CGRPを放出させる作用を有することがわかった。また、N－アセチルノイラミン酸の濃度が高いほど、放出されるCGRP量も有意に増加することがわかった（ｐ＜0.01）。 From the results, it was found that 1 to 100 μM N-acetylneuraminic acid has an action of stimulating sensory nerves and releasing CGRP. It was also found that the higher the concentration of N-acetylneuraminic acid, the greater the amount of CGRP released (p <0.01).
　限定的な解釈を望むものではないが、以上のことから、本願に係る経口育毛用組成物の効果は、CGRPの産生および放出により得られる可能性が考えられる。 Although a limited interpretation is not desired, it can be considered that the effects of the composition for oral hair restoration according to the present application can be obtained by the production and release of CGRP.
　試験例３：シアル酸の育毛作用
　6-8週齢のC57BL/6雄性マウス（日本SLC社）に対し、ケタラール 100 mg/kg、キシラジン 10 mg/kgとなるよう調製した混合液を腹腔内投与し、麻酔後、背部を２×４cmの大きさで剃毛した。次に、N－アセチルノイラミン酸を0.25 mg/mlおよび0.5 mg/mlになるように生理食塩水に溶解した。そして、これを体重10gあたり0.1 mlとなるよう胃ゾンデを用いて前述の剃毛マウスの胃内に1日1回強制投与した（すなわち、最終投与量は2.5 mg/kg/dayおよび5 mg/kg/dayである）。コントロールの剃毛マウスには、体重10gあたり0.1 mlとなるよう生理食塩水を投与した。なお、これらのN－アセチルノイラミン酸を強制投与したマウス及び生理食塩水のみ強制投与したコントロールのマウスは、当該強制投与以外は下記条件で飼育した。

明暗サイクル：照明１２時間
温度：２３度（+3 度,-3 度)
湿度：50%（+5%,-5%)
換気回数：約８回/時
飼料：MEQ固形飼料（オリエンタル酵母工業株式会社）
１ケージあたりの飼育匹数：最大７匹
水：滅菌水を自動給水

一週間後の各マウスの発毛状態を図２に示す。 Test Example 3: Hair growth effect of sialic acid 6-week-old C57BL / 6 male mice (Japan SLC) were administered intraperitoneally with a mixture prepared to give ketalal 100 mg / kg and xylazine 10 mg / kg After anesthesia, the back was shaved with a size of 2 × 4 cm. Next, N-acetylneuraminic acid was dissolved in physiological saline so as to be 0.25 mg / ml and 0.5 mg / ml. Then, this was forcibly administered once a day into the stomach of the aforementioned shaved mouse using a gastric sonde so as to be 0.1 ml per 10 g of body weight (ie, the final dose was 2.5 mg / kg / day and 5 mg / day). kg / day). The control shaved mouse was administered with physiological saline so as to be 0.1 ml per 10 g of body weight. The mice forcibly administered with these N-acetylneuraminic acids and the control mice forcibly administered with only saline were bred under the following conditions except for the forcible administration.

Light / dark cycle: Lighting 12 hours Temperature: 23 degrees (+3 degrees, -3 degrees)
Humidity: 50% (+5%,-5%)
Ventilation frequency: About 8 times / hour Feed: MEQ solid feed (Oriental Yeast Co., Ltd.)
Number of bred animals per cage: Up to 7 Water: Automatic supply of sterilized water

The hair growth state of each mouse after one week is shown in FIG.
　図２に示すように、コントロールのマウスはほとんど剃毛部分に毛は生えていないのに対し、N－アセチルノイラミン酸2.5 mg/kg/day投与群は幾分毛が生えて剃毛部分が小さくなっており、さらに、5 mg/kg/day投与群では、剃毛部分がほとんど見えなくなるほどにまで毛が生えていた。 As shown in FIG. 2, the control mice have almost no hair on the shaved part, whereas the N-acetylneuraminic acid 2.5 mg / kg / day group has some hair and has a shaved part. Furthermore, in the 5 mg / kg / day administration group, hair was grown to such an extent that the shaved portion was hardly visible.
　以上のことから、投与したN－アセチルノイラミン酸量に比例して、育毛効果が高まることがわかった。 From the above, it was found that the hair-growth effect was increased in proportion to the amount of N-acetylneuraminic acid administered.
　試験例４：マウスの皮膚カルシトニン遺伝子関連ペプチド（CGRP）およびインスリン様成長因子-Ｉ（IGF-I）濃度へのシアル酸の効果
＜皮膚サンプルの採取＞
N－アセチルノイラミン酸を0.5 mg/mlになるように生理食塩水に溶解した。そして胃ゾンデを用いて、これを体重10gあたり0.1 mlとなるよう 6-8週齢のC57BL/6雄性マウス（５匹）の胃内に1日1回強制投与した（すなわち、最終投与量は5 mg/kg/dayである）。コントロール群には同様にして体重10gあたり0.1 mlとなるよう生理食塩水を投与した（５匹）。 Test Example 4: Effect of sialic acid on mouse skin calcitonin gene-related peptide (CGRP) and insulin-like growth factor-I (IGF-I) concentrations <Skin sample collection>
N-acetylneuraminic acid was dissolved in physiological saline to a concentration of 0.5 mg / ml. Then, using a gastric sonde, this was forcibly administered once a day into the stomach of 6 to 8 week old C57BL / 6 male mice (5 mice) to 0.1 ml per 10 g of body weight (ie, the final dose was 5 mg / kg / day). Similarly, physiological saline was administered to the control group so as to be 0.1 ml per 10 g of body weight (5 animals).
　なお、これらのN－アセチルノイラミン酸を強制投与したマウス及び生理食塩水のみ強制投与したコントロールのマウスは、当該強制投与以外は試験例３に示した条件で飼育した。 The mice forcibly administered with these N-acetylneuraminic acids and the control mice forcibly administered with only saline were bred under the conditions shown in Test Example 3 except for the forcible administration.
　４週間後、ケタラール 100 mg/kg、キシラジン 10 mg/kgとなるよう調製した混合液を腹腔内投与して麻酔を行い、背部を剃毛し、皮膚を200mg（100mg×２）採取した。当該皮膚サンプルは直ちに液体窒素中で凍結し、－８０℃で保存した。 Four weeks later, a mixed solution prepared to give ketalal 100 mg / kg and xylazine 10 mg / kg was intraperitoneally anesthetized, the back was shaved, and 200 mg (100 mg × 2) of skin was collected. The skin sample was immediately frozen in liquid nitrogen and stored at -80 ° C.
  ＜皮膚CGRP濃度の測定＞
　2N酢酸２ml中に採取した皮膚サンプル100mgをいれ、ホモジネートした。ホモジネートしたサンプルは90℃の恒温槽に２０分間つけて、10000 rpm、4°Cで１０分間遠心分離し、上清を採取した。当該上清中のCGRP濃度を、enzyme immunoassay（EIA） kit（SPI-BIO, Massay Cedex, France）を用いて測定した。 <Measurement of skin CGRP concentration>
A 100 mg sample of skin taken in 2 ml of 2N acetic acid was placed in and homogenized. The homogenized sample was placed in a thermostat at 90 ° C. for 20 minutes, centrifuged at 10,000 rpm and 4 ° C. for 10 minutes, and the supernatant was collected. The CGRP concentration in the supernatant was measured using an enzyme immunoassay (EIA) kit (SPI-BIO, Massay Cedex, France).
　＜皮膚IGF-I濃度の測定＞
　1N酢酸２ml中に採取した皮膚サンプル100mgをいれ、ホモジネートした。
ホモジネートしたサンプルは10000 rpm、4°Cで１０分間遠心分離し、上清を採取した。当該上清中のIGF-I濃度を、EIA kit（Diagnostic Systems Laboratories Inc., Webster, TX）を用いて測定した。 <Measurement of skin IGF-I concentration>
100 mg of a skin sample collected in 2 ml of 1N acetic acid was added and homogenized.
The homogenized sample was centrifuged at 10,000 rpm and 4 ° C for 10 minutes, and the supernatant was collected. The IGF-I concentration in the supernatant was measured using EIA kit (Diagnostic Systems Laboratories Inc., Webster, TX).
　＜統計解析＞
  上述のようにして得た皮膚CGRP濃度及び皮膚IGF-I濃度のデータについて、平均値±標準偏差を求めた。さらに、Student’s t-testで解析してN－アセチルノイラミン酸投与群とコントロール群との比較を行った。結果を図３に示す。 <Statistical analysis>
For the data of skin CGRP concentration and skin IGF-I concentration obtained as described above, an average value ± standard deviation was obtained. Furthermore, the N-acetylneuraminic acid administration group and the control group were compared by analysis with Student's t-test. The results are shown in FIG.
　図３に示すように、N－アセチルノイラミン酸投与群では皮膚CGRP濃度がコントロール群のそれの約２．５倍にもなり、また、皮膚IGF-I濃度はコントロール群の約３倍にもなった。また、皮膚CGRP濃度及び皮膚IGF-I濃度のいずれにおいても、N－アセチルノイラミン酸投与群の方が有意に値が高かった（ｐ＜0.01）。 As shown in FIG. 3, the skin CGRP concentration in the N-acetylneuraminic acid administration group is about 2.5 times that of the control group, and the skin IGF-I concentration is about 3 times that of the control group. became. In addition, both the skin CGRP concentration and the skin IGF-I concentration were significantly higher in the N-acetylneuraminic acid administration group (p <0.01).
　このことから、シアル酸を経口投与することで、体内（特に皮膚）のCGRP濃度及びIGF-I濃度を大幅に上昇させられることが確認できた。 From this, it was confirmed that oral administration of sialic acid can significantly increase the CGRP concentration and IGF-I concentration in the body (particularly the skin).
各濃度のシアル酸存在下でマウス後根神経節細胞（DRG）を培養したときの、培養上清中に放出されるCGRPの濃度を示した図である。It is the figure which showed the density | concentration of CGRP released in a culture supernatant when a mouse | mouth dorsal root ganglion cell (DRG) is cultured in presence of sialic acid of each density | concentration. 背部を剃毛したマウスにシアル酸を経口投与して、育毛効果を検討した結果を示す図である。上図はコントロール群を、中図はシアル酸（N－アセチルノイラミン酸）2.5 mg/kg/day投与群を、下図はシアル酸（N－アセチルノイラミン酸）5.0 mg/kg/day投与群を、それぞれ示す。It is a figure which shows the result of having orally administered sialic acid to the mouse | mouth which shaved the back part, and examining the hair-growth effect. The upper figure shows the control group, the middle figure shows the sialic acid (N-acetylneuraminic acid) 2.5 mg / kg / day group, and the lower figure shows the sialic acid (N-acetylneuraminic acid) 5.0 mg / kg / day group Are shown respectively. シアル酸を経口投与したマウスの背部皮膚中のCGRP濃度及びIGF-I濃度を示すグラフである。It is a graph which shows the CGRP density | concentration and IGF-I density | concentration in the back skin of the mouse | mouth which orally administered sialic acid.

Claims (13)

  1. シアル酸、及び薬学的に許容される又は摂食可能な担体を含有する経口育毛用組成物。 An oral hair restoration composition comprising sialic acid and a pharmaceutically acceptable or ingestible carrier.
  2. シアル酸がＮ－アセチルノイラミン酸である、請求項１に記載の経口育毛用組成物。 The composition for oral hair restoration according to claim 1, wherein the sialic acid is N-acetylneuraminic acid.
  3. シアル酸を0.1～95重量％含有する、請求項１に記載の経口育毛用組成物。 The composition for oral hair restoration according to claim 1, comprising 0.1 to 95% by weight of sialic acid.
  4. 成人一日当たり0.01～1000mg/kgの量にて投与又は摂取される、請求項１に記載の経口育毛用組成物。
    The composition for oral hair restoration according to claim 1, which is administered or ingested in an amount of 0.01 to 1000 mg / kg per day for an adult.
  5. 医薬組成物である、請求項１に記載の経口育毛用組成物。 The composition for oral hair restoration according to claim 1, which is a pharmaceutical composition.
  6. 食品組成物である、請求項１に記載の経口育毛用組成物。
    The composition for oral hair restoration according to claim 1, which is a food composition.
  7. 育毛に有効な量のシアル酸を、育毛を望む人に経口投与又は摂取させる工程を含む、育毛方法。
    A method for hair growth comprising the step of orally administering or ingesting a person who desires hair growth with an amount of sialic acid effective for hair growth.
  8. シアル酸がＮ－アセチルノイラミン酸である、請求項７に記載の育毛方法。 The hair growth method according to claim 7, wherein the sialic acid is N-acetylneuraminic acid.
  9. シアル酸を、一日当たり0.01～1000mg/kgの量投与又は摂取させる、請求項７に記載の育毛方法。 The hair growth method according to claim 7, wherein sialic acid is administered or ingested in an amount of 0.01 to 1000 mg / kg per day.
  10. シアル酸の、経口育毛用組成物の製造のための使用。 Use of sialic acid for the production of a composition for oral hair restoration.
  11. シアル酸がＮ－アセチルノイラミン酸である、請求項１０に記載の使用。 Use according to claim 10, wherein the sialic acid is N-acetylneuraminic acid.
  12. 経口投与又は摂取により育毛するためのシアル酸。 Sialic acid for hair growth by oral administration or ingestion.
  13. 経口投与又は摂取により育毛するためのＮ－アセチルノイラミン酸。 N-acetylneuraminic acid for hair growth by oral administration or ingestion.
PCT/JP2009/053091 2008-05-28 2009-02-20 Oral composition for hair growth WO2009144977A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2010514394A JPWO2009144977A1 (en) 2008-05-28 2009-02-20 Oral hair growth composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008139525 2008-05-28
JP2008-139525 2008-05-28

Publications (1)

Publication Number Publication Date
WO2009144977A1 true WO2009144977A1 (en) 2009-12-03

Family

ID=41376865

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/053091 WO2009144977A1 (en) 2008-05-28 2009-02-20 Oral composition for hair growth

Country Status (2)

Country Link
JP (1) JPWO2009144977A1 (en)
WO (1) WO2009144977A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013522234A (en) * 2010-03-12 2013-06-13 ディーエスエム アイピー アセッツ ビー．ブイ． Supplementing sialic acid to the mother
CN104146885A (en) * 2014-07-14 2014-11-19 武汉中科光谷绿色生物技术有限公司 Application of N-acetylneuraminic acid hydrate in hair care product
KR20170045275A (en) * 2014-10-31 2017-04-26 가부시키 가이샤 파마푸즈 Hair growth promoter and use therefor

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08119986A (en) * 1994-10-25 1996-05-14 Nissin Food Prod Co Ltd Method for purifying sialic acid or its analog
JP2001192393A (en) * 2000-01-07 2001-07-17 Morinaga Milk Ind Co Ltd Endogenous sialidase-resistant lactone derivative- containing composition
JP2009073806A (en) * 2007-08-27 2009-04-09 Iriya Cosmetics Co Ltd Insulin-like growth factor-1 secretagogue

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2555389B2 (en) * 1987-12-21 1996-11-20 雪印乳業株式会社 Hair restorer
JP2006197914A (en) * 2005-01-21 2006-08-03 Takeshi Inaba Edible bird's nest-containing candy, and method for producing candy mixed with edible bird's nest
AU2008267279B2 (en) * 2007-06-25 2014-02-27 Dsm Ip Assets B.V. Novel prebiotics

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08119986A (en) * 1994-10-25 1996-05-14 Nissin Food Prod Co Ltd Method for purifying sialic acid or its analog
JP2001192393A (en) * 2000-01-07 2001-07-17 Morinaga Milk Ind Co Ltd Endogenous sialidase-resistant lactone derivative- containing composition
JP2009073806A (en) * 2007-08-27 2009-04-09 Iriya Cosmetics Co Ltd Insulin-like growth factor-1 secretagogue

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Sialic acid", KAGAKU DAIJITEN 4, vol. 30TH PRI, 15 February 1987 (1987-02-15), pages 46 - 47 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013522234A (en) * 2010-03-12 2013-06-13 ディーエスエム アイピー アセッツ ビー．ブイ． Supplementing sialic acid to the mother
CN104146885A (en) * 2014-07-14 2014-11-19 武汉中科光谷绿色生物技术有限公司 Application of N-acetylneuraminic acid hydrate in hair care product
KR20170045275A (en) * 2014-10-31 2017-04-26 가부시키 가이샤 파마푸즈 Hair growth promoter and use therefor
US10154684B2 (en) 2014-10-31 2018-12-18 Pharma Foods International Co., Ltd. Hair regrowth and growth promoter and use thereof
KR101966266B1 (en) * 2014-10-31 2019-04-05 가부시키 가이샤 파마푸즈 Hair regrowth and growth promoter and use thereof

Also Published As

Publication number Publication date
JPWO2009144977A1 (en) 2011-10-06

Similar Documents

Publication Publication Date Title
RU2548728C2 (en) Stevia extract or hair care steviol
KR102303570B1 (en) Agent or method for treatment and/or prevention of accelerated energy expenditure and/or diminished energy expenditure functionality
KR20080105023A (en) Nutraceutical composition for the treatment of muscle wasting
WO2011077800A1 (en) Hyperlipemia-ameliorating agent, anemia-ameliorating composition, uric-acid-level-reducing composition, and foods and beverages
WO2011096414A1 (en) Mitochondrial function improver
JP5592640B2 (en) Antistress agent containing lactic acid bacteria fermented royal jelly, method for producing the same, hypothalamus-pituitary-adrenocortical activity inhibitor, and sympathetic-adrenal medullary activity inhibitor
US20120309716A1 (en) Motor Function Improver
JP2022079551A (en) Composition for inhibiting myofibrosis
EP1767200A1 (en) Antiaging agent
WO2009144977A1 (en) Oral composition for hair growth
CN102273581A (en) Compound sweetener with high sweetness
EP4331601A1 (en) Food composition and pharmaceutical composition for preventing or alleviating sarcopenia, containing low-molecular-weight collagen as active ingredient
JP5394644B2 (en) Muscle enhancer containing asperroside or its analog
JP2019112328A (en) Compositions for improvement of circadian rhythm
KR101660834B1 (en) Anti-diabetic effects of Gypenoside 75
JP2022159178A (en) Anti-aging composition
US20200163854A1 (en) Life-extending agent, anti-aging agent, cosmetic, and food/beverage composition
WO2019146082A1 (en) Agent for improving autism spectrum disorder and mental disease
TWI830696B (en) Compositions for inhibiting muscle fiber degeneration
JP6071988B2 (en) Physical activity promoter
WO2010119804A1 (en) Anti-mental fatigue agent
JP2011063552A (en) Physical activity promoter
JP7206623B2 (en) Composition for prevention and improvement of glucose metabolism disorder
US11464824B2 (en) Peptide capable of improving cognitive function
EP4302765A1 (en) Composition for preventing, alleviating or treating sarcopenia, containing d-ribo-2-hexulose as active ingredient

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09754485

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2010514394

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09754485

Country of ref document: EP

Kind code of ref document: A1